A wearable non-invasive sonogenetic pacemaker

Cardiac pacemakers are critical for treating heart rhythm disorders, but traditional implants are associated with great risks and complications owing to their invasive nature. Here we introduce a wearable non-invasive ultrasound pacemaker (NUP) that activates engineered sonogenetic ion channels (MscL-G22S) to modulate cardiomyocytes, achieving spatiotemporally controlled precise cardiac pacing. In vitro studies on transfected human cardiomyocytes demonstrated synchronized calcium signalling and controlled responses to ultrasound stimulation. In vivo experiments in rats showed non-invasive pacing with high spatial precision (less than 1 mm) and frequency control (up to 9 Hz) stimulations in different heart chambers, restoring sinus rhythm in arrhythmic models. We validated long-term safety during daily activities in rats over 8 months. To assess translational potential, we show the genetic safety of NUP and demonstrated its feasibility for human-scale applications in ex vivo porcine models. With its compact, wearable design and imaging-guided stimulation, the NUP offers a non-invasive, safe and adaptable pacemaker solution for cardiac rhythm management.